Synthesis of some piperidine sugar uracil nucleosides with a 2,3′-substituted-imino bridge

Abstract

Base-catalysed isomerization of 2,3′-(substituted-imino)-1 -(3′-deoxy-β-D-lyxofuranosyl)uracils (1) to the corresponding pyranosyl analogues (2) was extended to the synthesis of analogous 2,3′-imino nucleosides having a piperidine sugar moiety. Trimesyluridine (3) with methylamine gave the 2,3′-methylimino-5′-O-mesyl-lyxofuranosyluracil (5). Compound (5) with ammonia, methylamine, orbenzylamine gave the corresponding5′-amino(6a),5′-methylamino(6b), or 5′-benzylaminoanalogue (6c), while the 3′,5′-di-O-mesyl derivative (4) of 2,2′-anhydrouridine with aniline gave the 2,3′-phenylimino analogues (6d), (7), and (8). Alkaline hydrolysis of compounds (6b and c) with 3M-NaOH-EtOH gave the corresponding piperidine sugar nucleosides (9a and b), while similar treatment of compound (6d) gave the piperidine (9c) and the dianilinolyxofuranosyluracil (10). On the other hand, the same reaction with compound (6a) yielded 3-hydroxypyridine (12) and N²-methylisocytosine (13)via thefuranosyl-to-piperidinyl isomerization, anomericbond fission, and elimination of compound (13) by [1,2]-hydride shift. 2′-O-Methyl analogue of (6a), compound (18b), with alkali gave N²-methyl-N²-(4-pyridino)isocytosine (19) exclusively, confirming the above mechanism for the formation of compounds (12) and (13) from (6a).